We decribed the preparation of adenine 1-oxide nucleotides by oxidation of the natural compounds with monopermaleic acid in aqueous solutions at neutral pH, with an overall yield after chromatographic purification between 75 and 80%. If irradiated, the adenine 1-oxide nucleotides undergo a photochemical rearrangement reaction, the main photoproducts in aqueous solution at alkaline pH being the corresponding isoguanine nucleotides. The modified ring vibration pattern of the 1-oxide analogues as well as the 13C chemical shift indicate a loss of aromaticity as compared to the natural compounds. Coupling constant measurements show that the dihedral angle between the 31POC and OC13C planes is around 180degree, i.e., trans, as in the natural adenine nucleotides. The modified adenine nucleotides were tested as potential substrates and/or inhibitors of mitochondrial processes, as substrates of varous phosphotransferases from mitochondria or cytosol, and as allosteric effectors in the reactions catalyzed by glutamate dehydrogenase and phosphofructokinase. Although the adenine 1-oxide nucleotides are not recognized by the translocase system of the inner mitochondrial membrane, they are good substrates for mitochondrial phosphotransferases located in the intermembrane space. Similarly, they participate in the phosphoryl group transfer reactions catalyzed by pyruvate kinase, phosphofructokinase, and hexokinase. As allosteric effectors, the modified nucleotides are less active than the natural compounds, probably because of a lower binding capacity to the allosteric sites of the regulatory enzymes.

No abstract

No abstract

The modified adenine nucleotides ATP-

Recent studies on escherichia coli bacteria cultivation, in which DNa thymine was replaced with 5-chlorouracil have refreshed the problem of understanding the changes to physical properties of DNa mono-I n a recent paper [1] it was reported that an international group of scientists working in xenobiology, a new brunch of life sciences, has succeeded in creating escherichia coli bacteria, in which DNA thymine was substituted with 5-chlorouracil of synthetic origin -a substance which is toxic to other organisms. Having successfully replaced the natural nucleotide base, the scientists began to test the vital functions of the modified organisms. They observed that such substitution did not affect the normal vital functioning of the bacteria and its ability to divide normally, but it was found that these investigated organisms were not capable to transfer the modified fragments of DNA to the bacteria with natural DNA (containing thymine), in other words they cannot change the normal organisms' genomes. Moreover, these mutated bacteria could not live even for one day without "toxic" environment, because 5-chlorouracil which is vital for them is not found in vivo. It was also revealed that even in environments where 5-chlorouracil is available in sufficient quantities, the lifetime of the new bacteria is several times lower than for similar bacteria with natural DNA.A reason for the reduced viability of bacteria with modified DNA can be modification of the AT pair donor-acceptor code in the DNA structure caused by the replacement of the methyl group of thymine with a chlorine atom. However, there is another possible mechanism for the effect of chlorination: changes in the conformational properties of nucleotides.Thus, the objective of our study is to find out what kind of changes in conformational and elastic properties of the monomers of this bacteria have been caused by the substitution of thymine with 5-chlorouracil. In addition to the potential usefulness to explain the peculiarities of life of the bacteria with modified DNA, solution of this problem has independent significance, because it allows tracing the relationship of the chemical structure and physical properties of biomolecules. materials and methodsAccording to the main task of the work a detailed quantum-mechanical conformational analysis of molecules of 5′-thymidylic acid (5TA)